N-[3-(1-{3-[(DIPHENYLACETYL)AMINO]PROPYL}-4-PIPERIDINYL)PHENYL]-2-METHYLPROPANAMIDE

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3-(1-{3-[(DIPHENYLACETYL)AMINO]PROPYL}-4-PIPERIDINYL)PHENYL]-2-METHYLPROPANAMIDE
• 英文别名: N-[3-[1-[3-[(2,2-diphenylacetyl)amino]propyl]piperidin-4-yl]phenyl]-2-methylpropanamide
• 化学式: C₃₂H₃₉N₃O₂
• 分子量: 497.681
• InChiKey: JFSBFNPKAYOILM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(3-piperidin-4-ylphenyl)isobutyramide 在 四丁基碘化铵 、 一水合肼 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 9.0h， 生成 N-[3-(1-{3-[(DIPHENYLACETYL)AMINO]PROPYL}-4-PIPERIDINYL)PHENYL]-2-METHYLPROPANAMIDE
  参考文献：
  名称：

  Synthesis and SAR Investigations for Novel Melanin-Concentrating Hormone 1 Receptor (MCH₁) Antagonists Part 1. The Discovery of Arylacetamides as Viable Replacements for the Dihydropyrimidinone Moiety of an HTS Hit

  摘要：

  Melanin-concentrating hormone (MCH) is involved in the regulation of feeding, water balance, energy metabolism, general arousal and attention state, memory, cognitive functions, and psychiatric disorders. Herein, two new chemical series exemplified by N-[5-(1-{3-[2,2-bis-(4-fluoro-phenyl)-acetylamino]-propyl}-piperidin-4-yl)-2,4-difluoro-phenyl]-isobutyramide (SNAP 102739, 5m) and N-[3-(l-{3-[(S)-2-(4-fluorophenyl)-propionylamino]-propyl}-piperidin-4-yl)-4-methylphenyl]-isobutyramide ((S)-6b) are reported. These compounds were designed to improve the pharmacokinetic properties of the high-throughput screening lead compound 1 (SNAP 7941). The MCH, receptor antagonists 5m and (S)-6b show reasonable pharmacokinetic profiles (rat bioavailability = 48 and 81%, respectively). Compounds 5m and (S)-6b demonstrated the inhibition of a centrally administered MCH-evoked drinking effect, and compound 5m exhibited oral in vivo efficacy in the rat social interaction model of anxiety, with a minimum effective dose = 0.3 mg/kg.

  DOI：

  10.1021/jm060381c

文献信息

• DNA encoding a human melanin concentrating hormone receptor (MCH1) and uses thereof
  申请人：——

  公开号：US20040038855A1

  公开（公告）日：2004-02-26

  This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors. This invention further provides a method of treating a subject suffering from urinary incontinence which comprises administering to the subject an amount of an MCH1 antagonist effective to treat the subject's urinary incontinence.

  该发明提供了编码人类MCH1受体的孤立核酸，纯化的人类MCH1受体，含有编码人类MCH1受体的孤立核酸的载体，含有这种载体的细胞，针对人类MCH1受体的抗体，用于检测编码人类MCH1受体的核酸探针，与编码人类MCH1受体的核酸的独特序列互补的反义寡核苷酸，表达编码正常或突变人类MCH1受体的转基因非人类动物，分离人类MCH1受体的方法，治疗与人类MCH1受体活性相关的异常的方法，以及确定化合物与哺乳动物MCH1受体结合的方法。该发明还提供了一种治疗患有尿失禁的受试者的方法，包括向受试者投予足以治疗受试者尿失禁的MCH1拮抗剂。
• Substituted alkyl amido piperidines
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US20040186103A1

  公开（公告）日：2004-09-23

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of reducing the body mass of a subject which comprises administering to the subject an amount of a compound of the invention effective to reduce the body mass of the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety.

  本发明涉及选择性拮抗黑色素浓集激素-1（MCH1）受体的化合物。该发明提供了一种包含本发明化合物的治疗有效量和药学可接受载体的制药组合物。本发明提供了一种由本发明化合物的治疗有效量和药学可接受载体组合而成的制药组合物。本发明还提供了一种制备包括本发明化合物的治疗有效量和药学可接受载体的制药组合物的方法。本发明还提供了一种减轻受试者身体质量的方法，该方法包括向受试者投与本发明化合物的有效量，以减轻受试者的身体质量。本发明还提供了一种治疗患有抑郁和/或焦虑症的受试者的方法，该方法包括向受试者投与本发明化合物的有效量，以治疗受试者的抑郁和/或焦虑症。
• Substituted anilinic piperidines as MCH selective antagonists
  申请人：Marzabadi R. Mohammad

  公开号：US20070043080A1

  公开（公告）日：2007-02-22

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier.

  本发明涉及选择性拮抗黑色素浓集激素-1（MCH1）受体的化合物。本发明提供了一种药物组合物，包括本发明化合物的治疗有效量和药学上可接受的载体。本发明提供了一种由本发明化合物的治疗有效量和药学上可接受的载体组成的药物组合物。本发明还提供了一种制备药物组合物的方法，包括将本发明化合物的治疗有效量和药学上可接受的载体组合。
• Synthesis and SAR Investigations for Novel Melanin-Concentrating Hormone 1 Receptor (MCH₁) Antagonists Part 1. The Discovery of Arylacetamides as Viable Replacements for the Dihydropyrimidinone Moiety of an HTS Hit
  作者：Yu Jiang、Chien-An Chen、Kai Lu、Irena Daniewska、John De Leon、Ron Kong、Carlos Forray、Boshan Li、Laxminarayan G. Hegde、Toni D. Wolinsky、Douglas A. Craig、John M. Wetzel、Kim Andersen、Mohammad R. Marzabadi

  DOI：10.1021/jm060381c

  日期：2007.8.1

  Melanin-concentrating hormone (MCH) is involved in the regulation of feeding, water balance, energy metabolism, general arousal and attention state, memory, cognitive functions, and psychiatric disorders. Herein, two new chemical series exemplified by N-[5-(1-3-[2,2-bis-(4-fluoro-phenyl)-acetylamino]-propyl}-piperidin-4-yl)-2,4-difluoro-phenyl]-isobutyramide (SNAP 102739, 5m) and N-[3-(l-3-[(S)-2-(4-fluorophenyl)-propionylamino]-propyl}-piperidin-4-yl)-4-methylphenyl]-isobutyramide ((S)-6b) are reported. These compounds were designed to improve the pharmacokinetic properties of the high-throughput screening lead compound 1 (SNAP 7941). The MCH, receptor antagonists 5m and (S)-6b show reasonable pharmacokinetic profiles (rat bioavailability = 48 and 81%, respectively). Compounds 5m and (S)-6b demonstrated the inhibition of a centrally administered MCH-evoked drinking effect, and compound 5m exhibited oral in vivo efficacy in the rat social interaction model of anxiety, with a minimum effective dose = 0.3 mg/kg.